Fu Xinping, Tao Lihua, Wang Pin-Yi, Cripe Timothy P, Zhang Xiaoliu
Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA.
Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA.
Oncotarget. 2018 Apr 20;9(30):21348-21358. doi: 10.18632/oncotarget.25096.
Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes of HSV, HSV-1 and HSV-2. The majority of oncolytic HSVs, including T-VEC which has recently been approved by the US Food and Drug Administration (FDA) for clinical use in treating late stage melanoma patients, are derived from HSV-1. Recently, we and others have developed several HSV-2 based oncolytic viruses. During our characterization of oncolytic viruses developed from both serotypes (Baco-1 from HSV-1 and FusOn-H2 from HSV-2), we noticed there is a subpopulation of cancer cells in which both viruses could infect but only FusOn-H2 could spread from cell to cell on monolayers. This observation prompted us to investigate the virus receptor expression profiles in these and other tumor cells. Our data show the following: 1) This subpopulation of tumor cells only express nectin-2, not the other two major receptors (HVEM or nectin-1). 2) Baco-1 grows to a higher titer than FusOn-H2 in this subpopulation of tumor cells, but the latter kills these tumor cells more efficiently than the former. 3) FusOn-H2 is effective at treating tumors formed from these tumor cells while Baco-1 is completely ineffective. Our results suggest that this subpopulation of tumor cells may be intrinsically resistant to the therapeutic effect of a HSV-1 based oncolytic virus but they remain sensitive to a HSV-2 based virotherapy.
单纯疱疹病毒（HSV）是众多为溶瘤目的而进行改造或优化的病毒之一。HSV有两种血清型，即HSV-1和HSV-2。大多数溶瘤性HSV，包括最近已获美国食品药品监督管理局（FDA）批准用于治疗晚期黑色素瘤患者的临床治疗的T-VEC，都源自HSV-1。最近，我们和其他研究人员开发了几种基于HSV-2的溶瘤病毒。在我们对这两种血清型所开发的溶瘤病毒（源自HSV-1的Baco-1和源自HSV-2的FusOn-H2）进行特性分析的过程中，我们注意到存在一部分癌细胞亚群，两种病毒都能感染该亚群癌细胞，但只有FusOn-H2能在单层细胞间进行细胞间传播。这一观察结果促使我们去研究这些及其他肿瘤细胞中的病毒受体表达谱。我们的数据显示如下：1）这一癌细胞亚群只表达nectin-2，不表达其他两种主要受体（HVEM或nectin-1）。2）在这一癌细胞亚群中，Baco-1的生长滴度高于FusOn-H2，但后者比前者更有效地杀死这些癌细胞。3）FusOn-H2对由这些癌细胞形成的肿瘤有治疗效果，而Baco-1则完全无效。我们的结果表明，这一癌细胞亚群可能对基于HSV-1的溶瘤病毒的治疗效果具有内在抗性，但它们对基于HSV-2的病毒疗法仍保持敏感。
